The broad objective of this research proposal is to seek a better understanding, at the molecular level, of the biochemical events which may be associated with the pathogenesis of emphysema, and thus provide a rational basis for the design of drugs that can be used for the effective treatment of this disease. Particular emphasis will be placed on the means whereby such inhibitors may be targeted to the lung tissue with minimal side effects on other tissues of the body. For this purpose, animals, in which emphysema has been induced by the administration of proteases known to be involved in the destruction of lung tissue (i.e. neutrophil elastase), will seve as the model system for testing the effectiveness of such inhibitors. The possible role of proteases secreted by alveolar macrophage will also be investigated.